Diethyl Carbonate → Ethyl 2-(pyrimidin-4-yl)acetate

HRID 332992Notes

Reaction equation

HRID 332992 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][C:12]1[CH:17]=[CH:16][N:15]=[CH:14][N:13]=1.[CH2:18]([O:20][C:21](=O)[O:22]CC)[CH3:19]>>[N:15]1[CH:16]=[CH:17][C:12]([CH2:11][C:21]([O:20][CH2:18][CH3:19])=[O:22])=[N:13][CH:14]=1

Participants

4

Reactant 3

HCID 7766Diethyl CarbonateHCID 189224-MethylpyrimidineHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 20295406Ethyl 2-(pyrimidin-4-yl)acetateYield 78.1%

Conditions

Temperature
-70 °C

Procedure

To a flask containing LiHMDS (32 mL, 31.89 mmol, 1.0 M in THF) at −70° C., was slowly added 4-methylpyrimidine (1.0 g, 10.63 mmol). After 5 min of stirring at −70° C., diethylcarbonate (1.93 mL, 15.95 mmol) was added, the reaction was slowly warmed to room temperature and stirred for 4 days. The reaction mixture was quenched by addition of 1 N HCl, neutralized with saturated aqueous NaHCO3 and extracted with EtOAc (3×). The combined organics were dried over Na2SO4, filtered, concentrated under reduced pressure and purified by flash chromatography on silica gel (0-100% EtOAc in hexanes) to give the title compound as a yellow oil (1.38 g, 78%). MS 167 (MH+).

Workup

  1. temperaturethe reaction was slowly warmed to room temperature
  2. stirringstirred for 4 days
  3. customThe reaction mixture was quenched by addition of 1 N HCl
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custompurified by flash chromatography on silica gel (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8e5cb3c6c4d641c6938b0428a1df94ef
Source dataset
uspto-grants-2014_11
Patent number
US08877922B2

Reaction notes

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